Dysplastic nevus syndrome

Dysplastic nevus syndrome is a cutaneous condition described in certain families, and characterized by unusual nevi and multiple inherited melanomas.:692 Dysplastic nevus syndrome is a cutaneous condition described in certain families, and characterized by unusual nevi and multiple inherited melanomas.:692 The CDKN2A gene is located on chromosome 9p21.3. Two main transcripts, isoforms '1' and '4', each contain three exons and span 7288 and 26740 bp, respectively. They encode proteins of 156 and 173 amino acids; isoform '1' encodes p16(INK4a), while isoform '4' encodes p14(ARF), a protein that is structurally unrelated to p16(INK4) but acts in cell cycle G1 control by stabilizing the tumor suppressor protein p53. Familial dysplastic nevus syndrome is inherited in an autosomal dominant manner. The penetrance for melanoma in kindreds with CDKN2A mutations is estimated at 58% to 92% by 80 years of age and varies with geography. The penetrance in CDKN2A mutation carriers for pancreatic cancer has been estimated to be 17% by 75 years of age. As noted above, there is wide variation in published estimates of the penetrance of CDKN2A mutations. The histopathologic characteristics of melanoma in FAMMM kindreds are not different from those seen in sporadic cases of melanoma and, thus, are not useful in diagnosing the syndrome. Superficial spreading melanoma (SSM) and nodular melanoma are the most frequently encountered histological melanoma subtypes in patients with CDKN2A mutations, which is consistent with the relative early age of onset. AMS has been described by multiple authors and institutions, and various definitions have been adopted. According to Newton et al., a scoring system allotting one point per feature establishes AMS with scores greater than or equal to 3. The features include: 1) two or more clinically atypical nevi, 2) more than 100 nevi in patients between 20 and 50 years of age, 3) more than 50 nevi in patients under 20 years of age or more than 50 years of age, 4) more than one nevus in buttocks or instep, 5) nevi on the anterior scalp, 6) one or more pigmented lesions in the iris.